The major focus of this grant renewal application is to further examine the reactivity and selectivity of a number of organic reactions in highly polar media such as 3.0-5.0 M lithium perchlorate-diethyl ether with applications to molecules of biological interest. During the course of this investigation we will continue to search for substitutes for lithium perchlorate in ether. In addition we remain focused on anions that are more weakly coordinating than perchlorate. This proposal is divided into three parts. The first section concentrates on studying the reaction of nucleophiles with oxabicyclo[2.2.1]heptanes and oxabicyclo [3.2.1]octanes i highly polar media. All the proposed studies will be of a fundamental nature in order to define the scope, limitations, and mechanism of this potentially very useful new reaction. Applications to the total synthesis of epothilone B, ulapualide A, aplyronine A, morphine, and the C(19)-C(27) aliphatic building block of rifamycin S are proposed. The second part of this grant application focuses on extending the ionic intramolecular Diels-Alder reaction in polar media for the construction of carbocyclic ring systems. Substrates will be examined wherein conformationally restricted tethered dienes are attached to the alpha, beta, and delta carbon atoms of the dienophiles. Application to syntheses of quadrone, magellaninone and pentalenene are proposed. In the third part of this grant application we will examine unique solvent systems (e.g. Li2B12H12-acetone, MgB12H12-acetone) in hopes of finding new opportunities for altering transition states while accelerating organic reactions. In addition we plan to examine lithium borates and lithium phosphates wherein the anions are chiral in hopes of catalyzing substitution reactions of allylic and benzylic acetates via single diastereomeric ion pairs which undergo facial discrimination in the attack by a nucleophile.